Proposed Pharmacovigilance Plan for H5N1 Influenza Virus Vaccine

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Proposed Pharmacovigilance Plan for H5N1
Influenza Virus Vaccine

• Patrick Caubel, MD, PhD
• Head of Pharmacovigilance North America
• February 27, 2007

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Background

• Planning for the prospect of pandemic influenza
  is one of the most effective steps to mitigate
  the impacts of such an event
• Vaccination remains a critical defense against
  pandemic influenza
• Vaccine safety monitoring is necessary
• Part of a comprehensive public health
  surveillance program

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Pharmacovigilance Plan Objectives

• Detect, evaluate and minimize risks due to the
  pandemic influenza vaccine
• Contributes to the benefit-risk evaluation in a
  pandemic situation
• Agree beforehand on
• Objectives for postmarketing safety surveillance
• Collaborative plan with key stakeholders
• Put in place an adequate system tailored to a
  pandemic situation to allow adequate responses

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Pharmacovigilance (PV) Planning

• PV activities have to be designed considering the
  following
• 1. Limited clinical data available
• 2. High volume of safety data anticipated within
  a short time frame
• 3. Increased public anxiety with AEs (adverse
  events) reported, regardless of causality
• 4. Limited personnel in industry and regulatory
  agencies
• 5. Possible disruption of pharmacovigilance
  systems
• Need for an on-going safety signal detection and
  evaluation
• Feasibility and effectiveness of the proposed
  actions/ measures need to be tested prior to the
  pandemic

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Pre-pandemic Standard PV Practices

• Applicable in pre-pandemic period
• Spontaneous reporting
• Aggregate reports at defined time intervals
• Signal detection and analysis
• Safety surveillance studies (possible cohort
  study in first responders)
• Passive collection of vaccine failure reports
• Objective Develop a better understanding of
  vaccine safety profile that could impact pandemic
  safety monitoring

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Pandemic Proposed PV Practices

• Applicable in pandemic situation
• Spontaneous reporting with a focus on special AEs
• Simplified aggregate reports
• Real time signal detection and analysis
• Safety surveillance studies (in early recipients
  after pandemic is declared)
• Passive collection of vaccine failure reports
• Objective Allocation of available resources on
  tasks critical for understanding the evolving
  benefit-risk profile in a pandemic situation

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Spontaneous ReportingData Collection

• Spontaneous reporting will remain the basis for
  safety evaluation
• One common simplified and targeted collection
  form could be used by all parties when the
  vaccination process begins
• Healthcare professionals and patients should be
  encouraged to report primarily serious adverse
  events, life-threatening events, adverse events
  of special interest (AESI), and deaths

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Spontaneous ReportingAdverse Events of Special
Interest

• All parties must consider a list of adverse
  events of special interest (AESI) for which a
  common case definition will be used in order to
  ensure harmonized safety assessment
• EMEA has proposed a list of AESI for pandemic
  vaccine surveillance

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Spontaneous Reporting Safety Database

• Rapid and open communication and information
  sharing between sanofi pasteur, other vaccine
  manufacturers and Authorities/Public Health
  Services (FDA, CDC, state and local authorities)
  is essential
• Electronic communication should be established
  prior to the pandemic period
• One single safety database dedicated to flu
  pandemic vaccines could be used and shared by all
  parties (VAERS database)

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Aggregate Reports

• Periodic Safety Update Reports (PSURs) are
  prepared at defined time intervals however,
  during the pandemic period due to limited
  resources, preparation and submission of PSURs
  may not be feasible
• Options
• Simplified PSURs
• Focusing on serious adverse events, deaths,
  life-threatening events, and AESI can be
  prepared.
• PSURs prepared on an ad-hoc basis upon request
  from Health Authority
• An aggregated PSUR will be submitted when the
  pandemic is declared finished

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Signal Detection and Analysis

• Crude inspection of single cases or line-listings
  not adequate
• Quantitative and automated data-mining methods
  should be considered (e.g. proportional reporting
  ratios, Bayesian methods)
• Modification of standard methods may be required
  (stratifications, use of appropriate comparator)
• May detect increase in incidence of AESI and
  support detection of unexpected AEs
• Should be tested with seasonal flu vaccines

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Monitoring for Vaccine Effectiveness

• There is no vaccine that is 100 effective
• Vaccine failure evaluation done through
  pharmacovigilance monitoring should not be used
  to assess vaccine effectiveness

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Safety Surveillance Studies

• Safety profile will remain unknown in numerous
  populations prior to vaccination campaign
• Consideration should be given to initiating
  cohort studies either prior to the pandemic
  (first responders, critical workers) or after the
  pandemic is declared (early recipients)
• Case-control studies using large population-based
  databases (e.g. Vaccine Safety Data Link) may be
  useful for rare serious AEs
• Should be coordinated by national and
  international public health agencies

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Summary

• Streamlining and prioritization are essential for
  early detection and communication of potential
  risks
• Pharmacovigilance plan and information-sharing
  system could be tested and harmonized during the
  forthcoming and subsequent flu seasons
• Proposed pharmacovigilance actions are part of an
  evolving plan to be refined with key
  stakeholders, together with roles and
  responsibilities
• Sanofi pasteur is committed to global pandemic
  preparedness

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Conclusion

• Safety of our vaccines are of paramount
  importance for sanofi pasteur.
• Sanofi pasteur is prepared to work with the
  Government on efficient methods of collecting
  safety and effectiveness data.